tbuckley/cabot-search huggingface dataset:
Abstract B058: The lincRNA Neat1 controls SWI/SNF occupancy to retain ductal cell identity in the pancreas
Authors: Emily Berry, Zamira Guerra Soares, Jennifer Twardowski, Wenjia Wang, Aram Hezel, Stephano S. Mello
Journal: Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths in the US and among the most fatal. Cancer originating from the ductal compartment often leads to the emergence of the highly aggressive basal subtype of PDAC. Defining the cellular and molecular origins of basal subtype PDAC would greatly improve our ability to devise strategies to treat patients with this aggressive form of PDAC. Towards this end, we have discovered that loss of the long intergenic non-coding RNA (lincRNA) Neat1 promotes ductal cell plasticity, dramatically inducing the formation of duct-derived preneoplastic lesions known as intraductal papillary mucinous neoplasms (IPMNs), and increasing the likelihood of basal subtype PDAC. Neat1 deficiency has a profound impact on chromatin organization and on the distribution of the SWI/SNF chromatin remodeling complex at the chromatin, suggesting that Neat1 maintains ductal cell identity via impacting SWI/SNF function. Probing for Brg1, a core component of the SWI/SNF complex, we demonstrated that Neat1 loss leads to decreased SWI/SNF binding at enhancer regions. This idea is further supported by the phenotypic similarities between mice deficient for Neat1 and Arid1a. We thus hypothesize that Neat1 and SWI/SNF are critical for the maintenance of ductal cell identity in the pancreas via controlling SWI/SNF-dependent enhancer activity and that loss of Neat1 increases ductal cell transformation and thus facilitates IPMN formation and progression to basal subtype PDAC. These studies will reveal both the biological role and mechanistic underpinnings of the lincRNA Neat1 in relationship with the SWI/SNF chromatin remodeling complexes. Our data suggest that Neat1 or SWI/SNF loss-of-function predisposes pancreatic ductal cells towards the most aggressive subtype of PDAC, laying critical groundwork for development of new diagnostic tools and therapeutic targets. Citation Format: Emily Berry, Zamira Guerra Soares, Jennifer Twardowski, Wenjia Wang, Aram Hezel, Stephano S. Mello. The lincRNA Neat1 controls SWI/SNF occupancy to retain ductal cell identity in the pancreas [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B058.
Patent Ductus Arteriosus and Development of Bronchopulmonary Dysplasia–associated Pulmonary Hypertension
Authors: Samuel J. Gentle, Colm P. Travers, Matthew Clark, Waldemar A. Carlo, Namasivayam Ambalavanan
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Background: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). The presence and duration of a patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. Methods: Retrospective case-control study among preterm infants 22w 0d to 28w 6d who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017-2020. Infants who were diagnosed with pulmonary hypertension (cases) by echocardiography were compared to infants without pulmonary hypertension (controls). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Generalized linear models adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. Results: 138 infants developed BPD alone and 82 infants developed BPD-PH. Following adjustment for differing covariates between groups, both PDA (aOR 4.29; 95% CI 1.89 – 9.77) and moderate to large PDA (aOR 4.15; 95% CI 1.78 – 9.64) remained significantly related to BPD-PH at discharge. By probit analysis each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (p<0.001) and 0.45 (p<0.001) respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both presence of and longer duration of ductus arteriosus patency was associated with the development of BPD-PH.
Abstract C061: Alternative polyadenylation regulates gene expression within the pancreatic cancer tumor microenvironment
Authors: Aditi H Chaubey, Michael E Feigin
Journal: Cancer Research (2022)

Abstract A characteristic of pancreatic ductal adenocarcinoma (PDAC) is that about 90% of its tumor volume can be made up of dense, fibrotic stroma. Multiple studies have shown that this dense stroma strongly influences disease progression and drug delivery. Amongst the cells that make up the stroma, Cancer Associated Fibroblasts (CAFs) are important regulators directly affecting cancer progression and therapeutic resistance. CAFs are a heterogeneous population, including inflammatory, myofibroblastic, and antigen-presenting CAFs, each with specific functional contributions to the cancer phenotype. While we have been able to define CAFs phenotypically, we lack a deeper understanding of the mechanisms underlying their transcriptional heterogeneity and ultimately their contribution in driving PDAC progression. Our lab has previously shown that 3’UTR-Alternative Polyadenylation (APA) is a key mechanism underlying gene dysregulation in PDAC. APA machinery makes use of multiple Poly A Sites (PAS) in a transcript and leads to the formation of distinct isoforms of mRNA with varying lengths, commonly referred to as short or long isoforms. This lengthening and shortening of mRNA modulates mRNA stability, protein expression, and localization, thus directly affecting cellular processes including proliferation, metastasis, and migration. We have now extended these findings to an analysis of APA events within the tumor microenvironment (TME). We find that 3’ UTR shortening is significantly associated with inflammatory CAFs (iCAFs), and that these APA events are correlated with gene expression changes in iCAF marker genes. We hypothesize that APA is a crucial driver of heterogeneity within the tumor microenvironment of PDAC. We have begun to elucidate the mechanisms underlying these gene regulatory changes in vitro using human-derived CAF cell lines via genetic and pharmacological inhibition of APA. Understanding these mechanisms may help us find druggable targets that may eventually affect the overall outcomes of PDAC patients. Citation Format: Aditi H Chaubey, Michael E Feigin. Alternative polyadenylation regulates gene expression within the pancreatic cancer tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C061.
Temporal and geographical variation in low carbon inhaler dispensing in England, 2016 to 2021: an ecological study
Authors: Jianghan Tian, Anita McGrogan, Matthew D Jones
Journal: Journal of the Royal Society of Medicine (2022)

Objectives In 2019–2020, four national recommendations were published in the United Kingdom to encourage use of low carbon inhalers. This study aimed to investigate whether these were associated with a change in primary care dispensing in England and to explore associations between geographical variation and clinical commissioning group (CCG) characteristics. Design Ecological study using aggregated publicly available data. Setting All CCGs in England (March 2016 to February 2021). Participants not applicable Main outcome measures Percentage of low carbon inhalers dispensed. Results The percentage of low carbon inhalers dispensed was 26.3% in 2020–2021 (of 8.8 million inhalers). This decreased over the study period for short-acting beta-agonist (SABA), inhaled corticosteroid (ICS) and ICS+long-acting beta-agonist (LABA) inhalers. The same trend was seen for LABA and ICS+LABA+long-acting muscarinic antagonist inhalers from 2019. The SABA and ICS classes were less often dispensed as low carbon inhalers (⁓6% versus 35–45%). Interrupted time series analyses found slight increases in low carbon inhaler percentage in the SABA, LABA and ICS classes after April 2019, which were soon erased by the long-term trend. There was also geographical variation, with the north-west, Birmingham and London consistently dispensing more low carbon inhalers. The presence of advice on climate change in CCG formularies/guidelines, the prevalence of asthma and population age profile were associated with significant variation in low carbon inhaler percentage for some classes. Conclusions The percentage of low carbon inhalers dispensed in England remains low and continues to decrease. Greater use of low carbon inhalers is achievable, but is more likely with locally implemented initiatives.
Suppression of CCL2 angiocrine function by adrenomedullin promotes tumor growth
Authors: Akiko Nakayama, Kenneth Anthony Roquid, András Iring, Boris Strilic, Stefan Günther, Min Chen, Lee S. Weinstein, Stefan Offermanns
Journal: The Journal of Experimental Medicine (2022)

Within the tumor microenvironment, tumor cells and endothelial cells regulate each other. While tumor cells induce angiogenic responses in endothelial cells, endothelial cells release angiocrine factors, which act on tumor cells and other stromal cells. We report that tumor cell–derived adrenomedullin has a pro-angiogenic as well as a direct tumor-promoting effect, and that endothelium-derived CC chemokine ligand 2 (CCL2) suppresses adrenomedullin-induced tumor cell proliferation. Loss of the endothelial adrenomedullin receptor CALCRL or of the G-protein Gs reduced endothelial proliferation. Surprisingly, tumor cell proliferation was also reduced after endothelial deletion of CALCRL or Gs. We identified CCL2 as a critical angiocrine factor whose formation is inhibited by adrenomedullin. Furthermore, CCL2 inhibited adrenomedullin formation in tumor cells through its receptor CCR2. Consistently, loss of endothelial CCL2 or tumor cell CCR2 normalized the reduced tumor growth seen in mice lacking endothelial CALCRL or Gs. Our findings show tumor-promoting roles of adrenomedullin and identify CCL2 as an angiocrine factor controlling adrenomedullin formation by tumor cells.
Protease‐Sensitive, VEGF‐Mimetic Peptide, and IKVAV Laminin‐Derived Peptide Sequences within Elastin‐Like Recombinamer Scaffolds Provide Spatiotemporally Synchronized Guidance of Angiogenesis and Neurogenesis (Adv. Healthcare Mater. 22/2022)
Authors: Fernando González‐Pérez, Matilde Alonso, Israel González de Torre, Mercedes Santos, José Carlos Rodríguez‐Cabello
Journal: Advanced Healthcare Materials (2022)

Elastin-Like Recombinamers In article 2201646 by José Carlos Rodriguez-Cabello and co-workers, a 3D model scaffold containing two cylindrical elastin-like recombinamer (ELR) hydrogels embedded in a slow-resorbable or nonprotease-sensitive ELR hydrogel that allow the independent spatiotemporal control of angiogenesis and neurogenesis in vivo, by the combination of protease-sensitive sequences, with fast and slow degradation kinetics, a VEGF-mimetic peptide (QK), and a laminin-derived peptide (IKVAV), is developed.
Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers (Adv. Healthcare Mater. 22/2022)
Authors: Ondřej Groborz, Kristýna Kolouchová, Jan Pankrác, Peter Keša, Jan Kadlec, Tereza Krunclová, Aneta Pierzynová, Jaromír Šrámek, Mária Hovořáková, Linda Dalecká, Zuzana Pavlíková, Petr Matouš, Petr Páral, Lenka Loukotová, Pavel Švec, Hynek Beneš, Lubomír Štěpánek, David Dunlop, Carlos V. Melo, Luděk Šefc, Tomáš Slanina, Jiří Beneš, Sandra Van Vlierberghe, Richard Hoogenboom, Martin Hrubý
Journal: Advanced Healthcare Materials (2022)

In Vivo Biodistribution Thermoresponsive polymers have found many promising (bio)medical applications, e.g. in situ thermogelling with controlled drug-release, polymer-supported brachytherapy, immunotherapy, and wound dressing. Despite the benefits of thermoresponsive polymers, their biodistribution and fate remained largely unknown, hindering their clinical use. Herein, Ondřej Groborz, Richard Hoogenboom, Martin Hrubý, and co-workers elucidate the pharmacokinetics and fate of thermoresponsive polymers in mice, in article 2201344. Finally, they perform a property-to-pharmacokinetics analysis. Cover art by Tomáš Belloň.
Coevolution of Myoelectric Hand Control under the Tactile Interaction among Fingers and Objects
Authors: Yuki Kuroda, Yusuke Yamanoi, Shunta Togo, Yinlai Jiang, Hiroshi Yokoi
Journal: Cyborg and Bionic Systems (2022)

The usability of a prosthetic hand differs significantly from that of a real hand. Moreover, the complexity of manipulation increases as the number of degrees of freedom to be controlled increases, making manipulation with biological signals extremely difficult. To overcome this problem, users need to select a grasping posture that is adaptive to the object and a stable grasping method that prevents the object from falling. In previous studies, these have been left to the operating skills of the user, which is extremely difficult to achieve. In this study, we demonstrate how stable and adaptive grasping can be achieved according to the object regardless of the user's operation technique. The required grasping technique is achieved by determining the correlation between the motor output and each sensor through the interaction between the prosthetic hand and the surrounding stimuli, such as myoelectricity, sense of touch, and grasping objects. The agents of the 16-DOF robot hand were trained with the myoelectric signals of six participants, including one child with a congenital forearm deficiency. Consequently, each agent could open and close the hand in response to the myoelectric stimuli and could accomplish the object pickup task. For the tasks, the agents successfully identified grasping patterns suitable for practical and stable positioning of the objects. In addition, the agents were able to pick up the object in a similar posture regardless of the participant, suggesting that the hand was optimized by evolutionary computation to a posture that prevents the object from being dropped.
Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study
Authors: Kristin H Bjørlykke, Hilde S Ørbo, Anne T Tveter, Ingrid Jyssum, Joseph Sexton, Trung T Tran, Ingrid E Christensen, Grete Birkeland Kro, Tore K Kvien, Jørgen Jahnsen, Ludvig A Munthe, Adity Chopra, David J Warren, Siri Mjaaland, Espen A Haavardsholm, Gunnveig Grødeland, Sella A Provan, John T Vaage, Silje Watterdal Syversen, Guro Løvik Goll, Kristin Kaasen Jørgensen
Journal: The Lancet Rheumatology (2022)
Comparison of RA Volumes Obtained Using the Standard Apical 4-Chamber and the RV-Focused Views
Authors: Pellegrino Ciampi, Luigi P. Badano, Diana R. Florescu, Francesco Villella, Michele Tomaselli, Camilla Torlasco, Mara Gavazzoni, Gianfranco Parati, Denisa Muraru
Journal: JACC. Cardiovascular imaging (2022)
Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial
Authors: Elias Jabbour, Nicholas J Short, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Pinaki Banerjee, Katayoun Rezvani, Xianli Jiang, Kun Hee Kim, Rashmi Kanagal-Shamanna, Joseph D Khoury, Keyur Patel, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Fadi G Haddad, Monica Kwari, Jennifer Thankachan, Ricardo Delumpa, Walid Macaron, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian
Journal: The Lancet Haematology (2022)
Coronary Atheroma Regression With Evolocumab in Stable and Unstable Coronary Syndromes
Authors: Stephen J. Nicholls, Yu Kataoka, Steven E. Nissen, Francesco Prati, Stephan Windecker, Rishi Puri, Thomas Hucko, Daniel Aradi, Jean-Paul R. Herrman, Renicus S. Hermanides, Bei Wang, Huei Wang, Julie Butters, Giuseppe Di Giovanni, Stephen Jones, Gianluca Pompili, Kathy Wolski, Peter J. Psaltis
Journal: JACC. Cardiovascular imaging (2022)
Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness
Authors: Wadah Ibrahim, Michael J. Wilde, Rebecca L. Cordell, Matthew Richardson, Dahlia Salman, Robert C. Free, Bo Zhao, Amisha Singapuri, Beverley Hargadon, Erol A. Gaillard, Toru Suzuki, Leong L. Ng, Tim Coats, Paul Thomas, Paul S. Monks, Christopher E. Brightling, Neil J. Greening, Salman Siddiqui, Rachel Munton, John Le Quesne, Alison H. Goodall, Hitesh C. Pandya, James C. Reynolds, Martha R. J. Clokie, Nilesh J. Samani, Michael R. Barer, Jacqueline A. Shaw
Journal: Science Translational Medicine (2022)

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analyzed exhaled breath samples from 277 participants presenting acute cardiorespiratory exacerbations and aged-matched healthy volunteers. Topological data analysis phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes (acute heart failure, acute asthma, acute chronic obstructive pulmonary disease, and community-acquired pneumonia). A multibiomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example, selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs.
Food-specific immunoglobulin A does not correlate with natural tolerance to peanut or egg allergens
Authors: Elise G. Liu, Biyan Zhang, Victoria Martin, John Anthonypillai, Magdalena Kraft, Alexander Grishin, Galina Grishina, Jason R. Catanzaro, Sharon Chinthrajah, Tina Sindher, Monali Manohar, Antonia Zoe Quake, Kari Nadeau, A. Wesley Burks, Edwin H. Kim, Michael D. Kulis, Alice K. Henning, Stacie M. Jones, Donald Y. M. Leung, Scott H. Sicherer, Robert A. Wood, Qian Yuan, Wayne Shreffler, Hugh Sampson, Veronika Shabanova, Stephanie C. Eisenbarth
Journal: Science Translational Medicine (2022)

ImmunoglobulinA (IgA) is the predominant antibody isotype in the gut, where it regulates commensal flora and neutralizes toxins and pathogens. The function of food-specific IgA in the gut is unknown but is presumed to protect from food allergy. Specifically, it has been hypothesized that food-specific IgA binds ingested allergens and promotes tolerance by immune exclusion; however, the evidence to support this hypothesis is indirect and mixed. Although it is known that healthy adults have peanut-specific IgA in the gut, it is unclear whether children also have gut peanut-specific IgA. We found in a cohort of non–food-allergic infants ( n = 112) that there is detectable stool peanut-specific IgA that is similar to adult quantities of gut peanut-specific IgA. To investigate whether this peanut-specific IgA is associated with peanut tolerance, we examined a separate cohort of atopic children ( n = 441) and found that gut peanut-specific IgA does not predict protection from development of future peanut allergy in infants nor does it correlate with concurrent oral tolerance of peanut in older children. We observed higher plasma peanut-specific IgA in those with peanut allergy. Similarly, egg white–specific IgA was detectable in infant stools and did not predict egg tolerance or outgrowth of egg allergy. Bead-based epitope assay analysis of gut peanut-specific IgA revealed similar epitope specificity between children with peanut allergy and those without; however, gut peanut-specific IgA and plasma peanut-specific IgE had different epitope specificities. These findings call into question the presumed protective role of food-specific IgA in food allergy.
A persistent neutrophil-associated immune signature characterizes post–COVID-19 pulmonary sequelae
Authors: Peter M. George, Anna Reed, Sujal R. Desai, Anand Devaraj, Tasnim Shahridan Faiez, Sarah Laverty, Amama Kanwal, Camille Esneau, Michael K.C. Liu, Faisal Kamal, William D.-C. Man, Sundeep Kaul, Suveer Singh, Georgia Lamb, Fatima K. Faizi, Michael Schuliga, Jane Read, Thomas Burgoyne, Andreia L. Pinto, Jake Micallef, Emilie Bauwens, Julie Candiracci, Mhammed Bougoussa, Marielle Herzog, Lavanya Raman, Blerina Ahmetaj-Shala, Stuart Turville, Anupriya Aggarwal, Hugo A. Farne, Alessia Dalla Pria, Andrew D. Aswani, Francesca Patella, Weronika E. Borek, Jane A. Mitchell, Nathan W. Bartlett, Arran Dokal, Xiao-Ning Xu, Peter Kelleher, Anand Shah, Aran Singanayagam
Journal: Science Translational Medicine (2022)

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.
The RTS,S malaria vaccine: Current impact and foundation for the future
Authors: James G. Beeson, Liriye Kurtovic, Clarissa Valim, Kwaku Poku Asante, Michelle J. Boyle, Don Mathanga, Carlota Dobano, Gemma Moncunill
Journal: Science Translational Medicine (2022)

The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of vaccine protection and longevity, implementation considerations, and future research needed to increase the vaccine's health impact, including vaccine modifications for higher efficacy and longevity of protection.
Positron emission tomography/magnetic resonance imaging of the sacroiliac joints and spine to monitor effects of anti–tumor necrosis factor therapy in axial spondyloarthritis: comment on the article by Bruckmann et al
Authors: Jerney de Jongh, Gerben J. C. Zwezerijnen, Maqsood Yaqub, Conny J. van der Laken
Journal: Arthritis & Rheumatology (2022)

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